1. Field of the Invention
The field of this invention is devices, methods and systems for collecting breast duct fluid from humans.
2. Description of the Background Art
For several decades significant members of the medical community dedicated to studying breast cancer have believed and shown that the cytological analysis of cells retrieved from nipple discharge from the breast milk ducts can provide valuable information leading to identifying patients at risk for breast cancer. Indeed Papanicolaou himself contributed to the genesis of such a possibility of a xe2x80x9cPapxe2x80x9d smear for breast cancer by analyzing the cells contained in nipple discharge. See Papanicolaou et al, xe2x80x9cExfoliative Cytology of the Human Mammary Gland and Its Value in the Diagnosis of Cancer and Other Diseases of the Breastxe2x80x9d Cancer (1958) March/April 377-409. See also Petrakis, xe2x80x9cPhysiological, biochemical, and cytological aspects of nipple aspirate fluidxe2x80x9d, Breast Cancer Research and Treatment 1986; 8:7-19; Petrakis, xe2x80x9cStudies on the epidemiology and natural history of benign breast disease and breast cancer using nipple aspirate fluidxe2x80x9d Cancer Epidemiology, Biomarkers and Prevention (January/February 1993) 2:3-10; Petrakis, xe2x80x9cNipple Aspirate Fluid in epidemiological studies of breast diseasexe2x80x9d, Epidemiologic Reviews (1993) 15:188-195. More recently, markers have also been detected in nipple fluid. See Sauter et al, xe2x80x9cNipple aspirate fluid: a promising non-invasive method to identify cellular markers of breast cancer riskxe2x80x9d, British Journal of Cancer 76(4):494-501 (1997). The detection of CEA in fluids obtained by a nipple blot is described in Imayama et al. (1996) Cancer 78: 1229-1234.
Breast cancer is believed to originate in the lining of a single breast milk duct in the breast; and additionally human breasts are believed to contain from 6 to 8 of these ducts. See Sartorius, JAMA 224 (6): 823-827 (1973). Sartorious describes use of hair-like single lumen catheters that are inserted into breast ducts using an operating microscope and the ducts were flushed with saline solution as described in Cassels, D Mar. 20th, 1973, The Medical Post, article entitled xe2x80x9cNew tests may speed breast cancer detectionxe2x80x9d. Sartorius et al, Contrast ductography for recognition and localization of benign and malignant breast lesions: an improved technique. pp. 281-300. In: Logan W W, ed. Breast Carcinoma New York, Wiley, 1977. After the fluid was infused, the catheter was removed because it was too small to collect the fluid, the breast was squeezed and fluid that oozed onto the nipple surface was removed from the surface by a capillary tube. Similarly, Love and Barsky, xe2x80x9cBreast-duct endoscopy to study stages of cancerous breast diseasexe2x80x9d, Lancet 348(9033):997-999, 1996 describes cannulating breast ducts with a single lumen catheter and infusing a small amount of saline, removing the catheter and squeezing to collect the fluid that returns on the nipple surface. The use of a rigid 1.2 mm ductscope to identify intraductal papillomas in women with nipple discharge is described in Makita et al (1991) Breast Cancer Res Treat 18: 179-188. It would be advantageous to develop methods and devices to collect the ductal fluid from within the duct.
Galactography, or contrast ductography has for years located breast ducts based on spontaneous nipple discharge, infused the ducts (using cannulas for this purpose) with contrast dye solutions, and taken x-ray pictures to determine the source of the discharge within the duct. See generally, The Breast: Comprehensive Management of Benign and Malignant Breast Diseases, Bland and Copeland eds. W. B. Saunders Co. Philadelphia Pa. 1991 pages 61-67.
Method and kits for obtaining fluid and cellular material from breast ducts 09/067,661 filed Apr. 28, 1998, and its CIP 09/301,058 filed Apr. 28, 1999 describe and claim infusing a small amount of fluid into the duct and collecting the fluid using a catheter. It would be beneficial to optimize the cells and fluid collected from this procedure.
U.S. Ser. No. 60/143,359 filed Jul. 12, 1999 describes and claims a multilumen catheter for collection of infused fluid. U.S. Ser. No. 60/143,476 filed Jul. 12, 1999 describes and claims devices and methods for accessing the lactiferous sinus of a breast duct. U.S. Ser. No. 60/122,076 filed Mar. 1, 1999 describes devices, methods and kits for accessing more than one breast duct at a time for delivering and/or retrieving agents or materials to and from more than one breast duct at the same time. Related applications are U.S. Ser. Nos. 60/143,476 and 60/143,359 both filed Jul. 12, 1999 and U.S. Ser. No. 60/134,613 filed May 18, 1999, and U.S. Ser. No. 60/114,048 filed Dec. 28, 1998, all of which are herein incorporated by reference in their entirety.
Osmotic agents including sugars that are poorly absorbed, for example lactulose or sorbitol, have been used as laxatives. See THE MERCK MANUAL OF MEDICAL INFORMATION, Berkow, Beers and Fletcher Eds, 1997 Merck Res. Lab., Whitehouse Station, N.J. pp. 522-523. The osmotic agent mannitol is available as an injectable, 25% (Physicians Desk Reference 1996) for a variety of indications (e.g. renal insufficiency, congestive heart failure). A mixture of sorbitol and mannitol is compared to distilled water as an irrigant during transurethral prostatectomy in Sargin et al, (1997) Int Urol Nephrol 29:575-80. Intracranial pressure therapy has been provided by solutions of mannitol, sorbitol or glycerol as described in Treib et al, (1998) Eur Neurol 40: 212-219. Osmotherapy for increased intracranial pressure comparing the use of mannitol and glycerol is discussed in Biestro et al, (1997) Acta Neurochir (Wien) 138: 725-32; discussion 732-3. Mannitol therapy for renal conditions is described generally in Better et al, (1997) Kidney Int 52:886-894, and use of the osmotic diuretic mannitol for renal protection is analyzed in Visweswaran et al, (1997) J Am Soc Nephrol 8: 1028-33. Use of mannitol during cardiac catheterization is described in Willerson et al, (1975) Circulation 51:1095-1100 and Kurnick et al, (1991) Am J Kidney Dis 17:62-8. The osmotic effects of polyethylene glycol are discussed in Schiller et al, (1988) Gastroenterology 94: 933-41. Raffinose is used for peritoneal dialysis as described in Kohan et al (1998) J Lab Clin Med 131: 71-6.
Relevant Literature
Hou et al, xe2x80x9cA simple method of Duct Cannulation and Localization for Galactography before Excision in Patients with Nipple Discharge.xe2x80x9d Radiology 1995; 195; 568-569 describes injecting a xe2x80x9csmall volume of sterile, water soluble contrast material . . . (0.5 ml-2.0 ml) . . . the catheter was taped on the breast or nipple . . . the contrast material was aspirated with the same syringe and gentle manual pressure was exerted on the breast to expel the opaque medium.xe2x80x9d
The use of a 0.4 mm flexible scope to investigate nipple discharge is described in Okazaki et al (1991) Jpn J. Clin. Oncol. 21:188-193 in which before the fiberoptic ductoscopy xe2x80x9ca lacrimal cannula was inserted [into the duct] for ductal washing by infusing 0.2 to 0.5 ml physiological saline twice or three times, citing also Okazaki et al Nyugan No Ringsho 4:587-594 (1989) (in Japanese).
A company called Diagnostics, Inc. formed in 1968, produced devices to obtain breast ductal fluid for cytological evaluation. The devices included a hair-like single lumen breast duct catheter to infuse fluid into a breast duct and the procedure dictated that after removal of the catheter oozing fluid was collected from the nipple surface with a capillary tube. The devices were sold prior to May 28, 1976 for the purpose of collecting breast ductal fluid for cytological evaluation.
A lacrimal irrigating cannula is described in U.S. Pat. No. 5,593,393 to inventors Trudell and Prouty. The cannula is graduated and used for insertion, dilation, probing and irrigating of the lacrimal drainage system of the eye. Lacrimal probes have been used to access breast ducts as depicted in The Breast: Comprehensive Management of Benign and Malignant Diseases (1991) vol 2, Bland and Kirby eds. W. B. Saunders Co, Philadelphia, Pa. pp. 63, FIGS. 3-26.
Patents and applications that describe use of a fixed support wire or support generally to reinforce the catheter include PCT publication WO 97/44084, PCT publication WO 97/44082, U.S. Pat. No. 5,221,255, JP 6-154334 (unexamined patent publication), U.S. Pat. No. 3,792,703 to Moorehead, U.S. Pat. No. 4,596,564 to Spetzler et al, U.S. Pat. No. 5,209,734 to Hurley et al, U.S. Pat. No. 5,456,674 to Bos et al, PCT publication WO 97/31677, PCT publication WO 94/07549, PCT publication WO 94/02197, European patent application EP 630 657 A1, European patent application EP 800 842 A1, Japanese unexamined patent publications JP 4-226675, JP 6-277289, and JP 6-277294, Japanese examined patent publication JP 3-4232, and PCT publication WO 97/47230.
Patents and publications that describe use of a very small atraumatic tip include U.S. Pat. No. 4,652,255 to Martinez, U.S. Pat. No. 5,246,430 to MacFarlane, PCT publication WO 97/37699, PCT publication WO 97/10015, PCT publication WO 94/07549, European patent application EP 729 766 A1, European patent application EP 643 979 A1, Japanese examined utility model publication JP 4-4730, and Japanese examined patent publications JP 1-14794, JP 61-24022, and JP 61-24023.
Patents and publications that describe and claim fluid collection catheters having a narrow distal portion and a larger diameter proximal portion with a shoulder therebetween include PCT publication WO 97/44084, PCT publication WO 97/44082, U.S. Pat. No. 5,221,255 to Mahurkar, JP 2,519,873 (U.S. Pat. No. 5,470,318), U.S. Pat. No. 4,553,957 to Williams et al, U.S. Pat. No. 4,652,255 to Martinez, U.S. Pat. No. 4,709,705 to Truglio, U.S. Pat. No. 5,451,208 to Goldrath, U.S. Pat. No. 5,246,430 to MacFarlane, PCT publication WO 97/48435, PCT publication WO 97/31677, PCT publication WO 95/20983, PCT publication WO 94/02197, European patent application EP 682 954 A2, European patent application EP 631 791 A1, Japanese examined patent publication JP 4-45186, Japanese unexamined utility model publication 6-77709, PCT publication WO 98/39046, and WO 97/47230.
Other patents or publications related in the art include the following: JP 5-184664 assigned to Terumo Corp. describes a catheter with a distal tip formed by heating; JP 2.631,320 Moriuchi et al, assigned to Terumo Corp. showing vascular catheter with multiple axial wire supports extending the length of the catheter; JP 3-264045 to Sato, assignee Terumo Corp. has a central reinforcement wire extending the length of intravascular catheter body; JP 61-268266 (WO 89/09079) to Hurley et al, assignee Sumitomo Bakelite (abandoned) depicting another wire reinforcement but in a uterine catheter; JP 6-502314 to Hurley et al, assignee Brigham and Women""s Hospital shows a spinal catheter with spinal wire reinforcement; JP 8-112354 to Takane depicts probe with isolate lumens and distal side ports; JP 5-237191 (EP 542246) to Pearsall, assignee Becton Dickinson shows rounded tips softer than the body of the catheter; JP 3-36363 (JP 4-516C) to Kamogawa, assignee Terumo Corp. is expired but has atraumatic tip with side ports and a single lumen; JP 2,531,583 to Onishi, assigned to Mitsubishi shows a catheter having a soft tip formed from polymer having a glass transition temperature at body temperature; JP 2,681,345 to Inoue, assignee Kitasato Supply shows insemination device with syringe; JP 5-184664 to Takeoka, assignee Terumo Corp. shows a single lumen rounded tip catheter with side ports; JP 58-46337 (JP 59-2345) to Fujimoto depicts a slidable stop on rectal catheter having side ports; and JP 58-146356 to Harris depicts an intrauterine catheter with shoulder stop. Patents and publications that describe breast access for purposes other than lavage include U.S. Pat. No. 5,800,534 to Jeter et al.
According to the present invention, a method for obtaining cellular material from a human breast milk duct comprises introducing a wash fluid to the breast milk duct, using a volume of at least 2 ml that is present within the duct for a preselected time, and collecting at least a portion of the introduced wash fluid from within the duct, with the portion of wash fluid carrying the cellular material. The preselected time is preferably less than one second, but will usually be in the range from one second to one hour. The wash fluid is preferably introduced to a volume of at least 2 ml, often at least 5 ml, and typically in the range between 5 ml and 25 ml, prior to collecting any of the wash fluid from the duct. The wash fluid is preferably introduced to a single breast milk duct and collected from the same breast milk duct without mixing with materials from other breast milk ducts. The method may further comprise separating cellular material from the collected fluid. The method may still further comprise examining the separated cellular material. The cellular material usually includes a substance selected from the group consisting of whole cells, cellular debris, proteins, nucleic acids, polypeptides, glycoproteins, lipids, fats, glycoproteins, small organic molecules, metabolites, and macromolecules.
Another aspect of the invention comprises a method for obtaining cellular material from a human breast milk duct including introducing a ductal access device having at least one lumen into a duct, introducing a wash fluid through the access device lumen into the milk duct, providing a volume of at least 2 ml to be present within the duct for a preselected time, and then collecting at least a portion of the wash fluid from the duct through the lumen of the access device. The method preferably further comprises massaging and squeezing the breast tissue after introducing the wash fluid but prior to and/or during collecting a portion of the wash fluid. Introducing the ductal access device typically comprises positioning a distal end of the device distal to the ductal sphincter in the breast duct. The access device preferably includes only a single lumen that extends into the duct. The wash fluid is preferably introduced to a volume of at least 2 ml prior to collecting any of wash fluid from the duct. The preselected time can be less than one second, but will usually be in the range from one second to one hour. The wash fluid can be introduced to a single breast milk duct and collected from the same breast milk duct without mixing with materials from other breast milk ducts. The method may still further comprise separating cellular material from the collected fluid. The method may still further comprise examining the separated cellular material. The cellular material is usually a substance selected from the group consisting of whole cells, cellular debris, proteins, nucleic acids, polypeptides, glycoproteins, lipids, fats, glycoproteins, small organic molecules, metabolites, and macromolecules.
Another aspect of the invention is a method for obtaining cellular material from a human breast milk duct comprising introducing a wash fluid to the breast milk duct, providing that the wash fluid is present within the duct for a preselected time, and collecting at least a portion of the introduced wash fluid from within the duct, where the portion carries the cellular material; the wash fluid is introduced to a single breast milk duct and collected from the same breast milk duct without mixing with materials from other breast milk ducts. The volume of wash fluid can be at least 2 ml. The preselected time can be less than one second or can be in a range from one second to one hour. The method can further comprise separating cellular material from the collected fluid. The method can also further comprise examining the separated cellular material. The cellular material can be a substance selected from the group consisting of whole cells, cellular debris, nucleic acids, lipids, protein metabolites, small organic molecules, and macromolecules.
An aspect of the invention is another method for obtaining cellular material from a human breast milk duct comprising introducing a ductal access device having at least one lumen into a duct, introducing a wash fluid through the access device lumen into the milk duct, where the wash fluid is present within the duct for a preselected time, and collecting at least a portion of the wash fluid from the duct through the lumen of the access device; the wash fluid is introduced to a single breast milk duct and collected from the same breast milk duct without mixing with materials from other breast milk ducts. The volume of wash fluid can be at least 2 ml. The preselected time can be less than one second or in a range from one second to one hour. The method can further comprise separating cellular material from the collected fluid, and the separated material can be examined. The cellular material can be a substance selected from the group consisting of whole cells, cellular debris, nucleic acids, lipids, protein metabolites, small organic molecules, and macromolecules.
An aspect of the invention is a kit comprising a ductal access device; and instructions for use setting forth a method provided above comprising introducing a ductal access device having at least one lumen into a duct.
An aspect of the invention is a ductal access device comprising an access tube having a distal end, at least one lumen, and dimensions which permit introduction of the distal end through a ductal orifice and positioning a distal end distal to the ductal sphincter of a human breast. The device can further comprise means on the access tube for positioning the distal end distal to the ductal sphincter. The positioning means can comprise length indicia on the tube which permit a user to determine the depth to which the distal end of the tube has been introduced. The positioning means can comprise a stop element formed or attached to the tube; the stop will have dimensions which prevent further insertion of the tube into the duct and the stop is positioned on the tube so that the distal tip will be located distal to the ductal sphincter when the device is fully inserted up to the stop. The stop element can comprise a collar affixed to or formed on an exterior surface of the tube. The device can comprise means for anchoring the device to the breast. The device can include a receiving portion comprising a water tight seal for receiving the dilator. The stop element can comprise a hub attached to a proximal end of the tube, where the hub has a width which is greater than the diameter of the tube so that a shoulder is formed at a junction between the tube and the hub. The positioning means can comprise a nob on the access tube having an increase diameter for anchoring the tube in the lactiferous sinus once the nob has passed the sphincter and rests in the sinus. The access tube can have an outer diameter of 0.05 inches (or 1.27 mm) or less. The access tube can have an outer diameter of 0.010 inches (or 0.254 mm) or greater. The outer diameter can be in the range from 0.010 inches (or 0.254 mm) to 0.050 inches (or 1.27 mm). The access tube can have a lumen diameter 0.007 inches (or 0.178 mm) or greater. The access tube can have a lumen diameter in the range from 0.007 inches (or 0.178 mm) to 0.047 inches (or 1.19 mm). The access device can further comprise an infusion connector providing a fluid flow path into the lumen of the tube; and a collection connector providing a fluid outlet path from the lumen of the tube; the infusion and collection connectors are isolated from each other so that the fluid may be infused through the infusion connector and simultaneously removed through the collection connector. The device can further comprise a dilator removably received in the access tube and having a distal tip which is positionable through the access tube to extend from the distal end of the device. The dilator can have an outer diameter of 0.024 inches (or 0.61 mm) or less. The dilator can be tapered. A receiving portion of the device for receiving the dilator can comprise a water-tight seal.
An aspect of the invention is a ductal access system comprising a ductal access device as described and a container holding a premeasured volume of ductal wash fluid. The container can comprises a syringe for connection to the first side port. The pre-measured volume can be in the range from 2 ml to 100 ml. The ductal access fluid is can be selected from the group consisting of saline, phosphate buffered saline, a nonabsorbable fluid, an isotonic solution, an osmotic solution, a hypotonic solution, and a hypertonic solution.
A further aspect of the invention is a ductal access device comprising an access tube having a distal end, a single lumen, and dimensions which permit introduction of the distal end through a ductal orifice and positioning a distal end of the device distal to the ductal sphincter, an infusion connector providing a fluid flow path into the lumen of the access tube, and a collection connector providing a fluid outlet path from the lumen of the access tube; the infusion and collection connectors being isolated from each other so that fluid may be infused through the infusion connector and simultaneously removed through the collection connector. The tube has an outer diameter of 0.010 inches (or 0.254 mm) or greater or the tube has an outer diameter of 0.050 inches (or 1.27 mm) or less, or the outer diameter can be in the range from 0.010 inches (or 0.254 mm) to 0.50 inches (or 1.27 mm).
The access tube has a lumen diameter 0.007 inches (or 0.178 mm) or greater, or a lumen diameter in the range from 0.007 inches (or 0.178 mm) to 0.047 inches (or 1.19 mm). The device can further comprise means on the access tube positioning a distal end of the device distal to the ductal sphincter. The positioning means can comprise length indicia on the tube which permit a user to determine the depth to which the distal end of the tube has been introduced. The positioning means comprises a stop element formed or attached to the tube, and the stop has dimensions which prevent further insertion of the tube into the duct; the stop is positioned on the tube so that a distal end of the distal tip is positioned distal to the ductal sphincter. The stop element comprises a collar affixed to or formed on an exterior surface of the tube. The stop element can comprise a hub attached to a proximal end of the tube, where the hub has a width which is greater than the diameter of the tube so that a shoulder is formed at a junction between the tube and the hub. The positioning means can comprise a nob on the access tube having an increased diameter for anchoring the distal portion of the tube distal to the sphincter once the nob has passed the sphincter. The device can comprise means for anchoring the device to the breast. The device can additionally comprise a dilator removably received in the access tube and having a distal tip which is positionable through the access tube to extend from the distal end of access device. The dilator can have an outer diameter of 0.024 inches (or 0.61 mm) or less. The dilator can be tapered. A receiving portion of the device for receiving the dilator an comprise a water-tight seal.
An aspect of the invention is a ductal access system comprising a ductal access device as just described and a container holding a premeasured volume of ductal wash fluid. The container can comprise a syringe for connection to the first side port. The premeasured volume can be in the range from 2 ml to 100 ml. The ductal access fluid can be selected from the group consisting of saline, phosphate buffered saline, a nonabsorbable fluid, an isotonic solution, an osmotic solution, a hypotonic solution, and a hypertonic solution.
An aspect of the invention is a ductal access device comprising a hub having an internal elongate manifold, a lower port at a bottom of the manifold, and first and second side ports spaced above the lower port; and an access tube having a distal end, a proximal end, a lumen, and dimensions which permit introduction of the distal end through a ductal orifice and a positioning a distal end of the device distal to the ductal sphincter of the human breast, provided also that the proximal end of the tube is attached to the lower port of the hub. The first and second side ports can be at the same level relative to the lower port. The first side port can be below the second side port. The access tube can have an outer diameter of 0.010 inches (or 0.254 mm) or greater. The access tube can have an outer diameter of 0.50 inches (or 1.27 mm) or less. The outer diameter can be in the range from 0.010 inches (or 0.245 mm) to 0.50 inches (or 1.27 mm). The access tube can have a lumen diameter 0.007 inches (0.178 mm) or greater, or a lumen diameter in a range from 0.007 inches (0.178 mm) to 0.047 inches (1.19 mm). The device can have an infusion tube connected to the first port of the hub; and a collection tube connected to the second port of the hub. The device can further comprise a means for controlling a flow of fluid through the infusion tube, a means for controlling a flow of fluid through the collection tube, or both a means for controlling a fluid flow through the infusion lumen and a means for controlling a fluid flow through the collection lumen. The fluid control means can comprise compressable lumens or the fluid control means can comprise stopcocks on each lumen. The hub or manifold can have a volume in the range from 0.01 ml to 1.0 ml. The first side port can be spaced above the lower port by a distance less than 5 mm and the second side port can be spaced above the first side port by a distance in the range from 0.10 mm to 5 mm. The device can further comprise a dilator removably received in the hub and having a distal tip which is positionable through the access tube to extend from the distal end of the device. The dilator can have an outer diameter of 0.024 inches (or 0.61 mm) or less. The dilator can be positionable through the hub manifold and into the lumen of the access tube. The dilator can be tapered. A receiving portion of the hub for receiving the dilator can comprise a water-tight seal. The device can further comprise a means on the access tube for positioning the distal end of the access tube distal to the ductal sphincter. The positioning means can comprise length indicia on the tube which permit a user to determine the depth to which the distal end of the tube has been introduced. The positioning means can comprise a stop element formed or attached to the tube; the stop has dimensions which prevent further insertion of the tube into the duct and the stop is positioned on the tube so that the distal tip will be located distal to the ductal sphincter when the device is fully inserted up to the stop. The stop element can comprises a collar affixed to or formed on an exterior surface of the tube. The stop element can comprise a hub attached to a proximal end of the tube, where the hub has a width which is greater than the diameter of the tube so that a shoulder is formed at a junction between the tube and the hub. The device can further comprise a means for anchoring the device to the breast. The positioning means can comprise a nob on the access tube having an increased diameter for anchoring the tube distal to the ductal sphincter once the nob has passed the sphincter and rests distal to it.
An aspect of the invention is a ductal access system comprising a ductal access device as just described and a container holding a premeasured volume of ductal wash fluid. The container can comprise a syringe for connection to the first side port. The pre-measured volume can be in the range from 2 ml to 100 ml. The ductal access fluid can be selected from the group consisting of saline, phosphate buffered saline, a nonabsorbable fluid, an isotonic solution, an osmotic solution, a hypotonic solution, and a hypertonic solution.
An aspect of the invention provides a ductal access catheter comprising a catheter body having a distal end and a proximal end and including at least a distal portion and a proximal portion wherein the distal portion has a cross-sectional geometry which can be inserted through a ductal orifice into a ductal lumen of a human breast; wherein the proximal portion has a cross-sectional geometry which inhibits insertion through the ductal orifice and into the ductal lumen; and wherein the catheter body has at least an infusion lumen and an collection lumen each of which has a distal port near a distal end of the distal portion and a proximal connector near a proximal end of the proximal portion. The device can further comprise a means for controlling a flow of fluid through the infusion lumen, a means for controlling a flow of fluid through the collection lumen, or both a means for controlling a fluid flow through the infusion lumen and a means for controlling a fluid flow through the collection lumen. The fluid control means can comprise compressable lumens, or the fluid control means can comprise stopcocks on each lumen.
The distal portion of the catheter body can be stiffened over at least a part of its length to facilitate insertion through the ductal orifice and into the ductal lumen. The stiffened distal portion of the catheter body has an average bending stiffness in the range from about 0.010 inch-lbs to about 0.5 inch-lbs. The stiffening member is disposed in the distal portion of the catheter body.
The distal portion of the catheter body has a maximum width in the range from 0.016 inches to 0.022 inches (0.56 mm) and the proximal portion of the catheter body has a minimum width in the range from 0.023 inches (0.58 mm) to 0.028 inches (0.71 mm). The distal portion of the catheter body has a generally tubular structure with a diameter in the range from 0.010 inches (0.254 mm) to 0.020 inches (0.51 mm) and the proximal portion of the catheter body has a generally tubular structure with a diameter in the range from 0.030 inches (0.762 mm) to 0.10 inches (0.254 mm) and wherein the proximal diameter is greater than the distal diameter by at least 0.010 inches (or 0.254 mm). At least one of the distal collection port and the distal infusion portion can be disposed on a side of the distal portion of the catheter body. The distal collection port and the distal infusion port can both be located on the side of the distal portion of the catheter body. The distal collection port and the distal infusion port can be axially aligned. The distal collection port and the distal infusion port can be axially spaced apart. The catheter body can include an atraumatic distal tip. The tip can be composed of a soft polymeric material, have a diameter in the range from about 0.008 inches (0.20 mm) to about 0.035 inches (0.89 mm), and a length in the range from about 0.25 cm to about to 2.5 cm.
The invention further provides a ductal access catheter comprising a catheter body having a distal end and a proximal end and including at least a distal portion and a proximal portion; wherein the distal portion has a cross-sectional geometry which can be inserted through a ductal orifice into a ductal lumen of a human breast; wherein the distal portion of the catheter body is stiffened over at least a part of its length to facilitate insertion through the ductal orifice and into the ductal lumen; and wherein the catheter body has at least an infusion lumen and an collection lumen each of which has a distal port near a distal end of the distal portion and a proximal connector near a proximal end of the proximal connector. The stiffened distal portion of the catheter body can have an average bending stiffness in the range from about 0.010 inch-lbs to about 0.5 inch-lbs. The proximal portion can have a cross-sectional geometry that inhibits insertion through the ductal orifice and into the ductal lumen.
The invention also provides a ductal access catheter comprising a catheter body having a distal end and a proximal end and including at least a distal portion and a proximal portion; wherein the distal portion has a cross-sectional geometry which can be inserted through a ductal orifice into a ductal lumen of a human breast; and wherein the catheter body has at least an infusion lumen and an collection lumen each of which has a distal port near a distal end of the distal portion and a proximal connector near a proximal end of the proximal connector; and wherein the distal collection port and the distal infusion port are both located on the side of the distal portion of the catheter body. The distal collection port and the distal infusion port can be axially aligned. The distal collection port and the distal infusion port can be axially spaced apart. The proximal portion can have a cross-sectional geometry that inhibits insertion through the ductal orifice and into the ductal lumen.
Another aspect of the invention is a method for lavage of a ductal network in a human breast comprising providing a multi-lumen catheter as just described and inserting the distal portion of the catheter through a ductal orifice and into a distal lumen of the ductal network; introducing a wash fluid through the infusion lumen into the ductal network; and withdrawing the wash fluid and substances borne by the wash fluid from the ductal network through the collection lumen.
Another aspect of the invention is a system comprising a multi-lumen catheter as just described and instructions for use setting forth a method for lavage of a ductal network in a human breast including introducing a wash fluid through the infusion lumen into the ductal network and withdrawing the wash fluid and substances borne by the wash fluid from the ductal network through the collection lumen.
The agent infused into the duct can comprise a non-absorbable fluid and/or an oncotic agent and/or an osmotic agent. The agent can be soluble. The agent can comprise a molecule that is a protein, a colloid, a sugar, or a polymer. The agent can be mannitol, sorbitol, glucose, glycerol, sucrose, raffinose, fructose, lactulose, sodium chloride, polyethyleneglycol (PEG), maltodextrin, dextran (e.g. dextran 70), hydroxyethyl starch, fluid gelatin, or a synthetic colloid. The agent can comprise a protein and the protein can be a binding protein or an antibody. The binding protein can be albumin. Administering can comprise administering locally, and local administration can comprise administering intraductally. A system for increasing or standardizing an amount of fluid collectable from a milk duct of a breast can comprise infusing a nonabsorbable fluid and/or an osmotic agent and/or an oncotic agent into the ductal lumen, a medical tool for delivering the agent to the ductal lumen, and instructions for use.